Pennarossa Georgia, Ghiringhelli Matteo, Gandolfi Fulvio, Brevini Tiziana A L
Laboratory of Biomedical Embryology, Department of Health, Animal Science and Food Safety and Center for Stem Cell Research, Università degli Studi di Milano, Milan, Italy.
Sohnis Research laboratory for Cardiac Electrophysiology and Regenerative Medicine, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
Methods Mol Biol. 2022;2436:157-165. doi: 10.1007/7651_2021_398.
Long-segment airway stenosis as well as their neoplastic transformation is life-threatening and still currently represent unsolved clinical problems. Indeed, despite several attempts, definitive surgical procedures are not presently available, and a suitable tracheal reconstruction or replacement remains an urgent clinical need. A possible innovative strategic solution to restore upper airway function may be represented by the creation of a bioprosthetic trachea, obtained through the combination of tissue engineering and regenerative medicine.Here we describe a two-step protocol for the ex vivo generation of tracheal segments. The first step involves the application of a decellularization technique that allows for the production of a naturally derived extracellular matrix (ECM)-based bio-scaffold, that maintains the macro- and micro-architecture as well as 9 the matrix-related signals distinctive of the original tissue. In the second step chondrocytes are seeded onto decellularized trachea, using a rotating bioreactor to ensure a correct scaffold repopulation.This multi-step approach represents a powerful tool for in vitro reconstruction of a bioengineered trachea that may constitute a promising solution to restore upper airway function. In addition, the procedures here described allow for the creation of a suitable 3D platform that may find useful applications, both for toxicological studies as well as organ transplantation strategies.
长节段气道狭窄及其肿瘤转化会危及生命,目前仍是尚未解决的临床问题。事实上,尽管进行了多次尝试,但目前尚无确定性的外科手术方法,合适的气管重建或置换仍是迫切的临床需求。通过组织工程和再生医学相结合获得生物人工气管,可能是恢复上气道功能的一种创新性战略解决方案。在此,我们描述了一种用于气管节段体外生成的两步方案。第一步涉及应用去细胞化技术,以生产基于天然衍生细胞外基质(ECM)的生物支架,该支架保留了原始组织的宏观和微观结构以及与基质相关的独特信号。第二步,使用旋转生物反应器将软骨细胞接种到去细胞化气管上,以确保支架正确地重新填充细胞。这种多步骤方法是体外重建生物工程气管的有力工具,可能是恢复上气道功能的一种有前景的解决方案。此外,本文所述的方法允许创建一个合适的三维平台,该平台可能在毒理学研究以及器官移植策略中找到有用的应用。